Biotech Values

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MNTA Analysis of carbohydrate structure

It might be hard to get a 3D crystal structure of low molecular weight heparin since it is a heterogenous mixture of similar materials, so may not produce nice crystals easily. Besides, MNTA touts their ability to characterize carbohydrates/sugars/glycosylation, so presumably they've done everything they can already.

Yes, certain types of glycoslation can create immune responses, such as the hyperacute transplant rejection observed when people first tried putting pig organs into humans. (It turns out that swine have an enzyme humans don't so produce a type of glycosyl group on their cells that is utterly alien to humans, and causes an extreme immune response within minutes.) Many sugars however do not induce much in the way of an immune response, so it can be difficult to produce antibodies that bind specific sugar types tightly.

MNTA emphasized in the conference call that they didn't know what the FDA was concerned about nor what further information they wanted to see. MNTA said there could be dozens of things the FDA wanted to ask about, and they would have to wait until they learned more.

Since MNTA has already tested this in humans, at least to get PK/PD data, they should know already if there was a severe allergic reaction. It is also possible that impurities or contaminants in the manufacturing process could cause problems, but presumably the FDA would have addressed this issue already.

The FDA told MNTA that all companies wanting to market generic Lovenox would have to provide information about whether immunogenicity was an issue. It is possible that this means that one of the other companies produced data that indicates that this could be a concern, so the FDA is asking all the companies to check for it. Or it could be that the FDA is getting extra cautious for some reason.

One of the first analysts to ask questions on the conference call said something along the lines of:
"This is like a 'When did you stop beating your wife?' question. How do you know that your generic product is no more immunogenetic than the branded product when there is no data on what is normal for the branded product?"

It would be interesting if immunogenicity data will have to be collected for all potential generic drugs submitted via an ANDA.

And, wow, MNTA first filed the ANDA in August of 2005, and this is the first time the FDA mentioned immunogenicity? And does it always take this long for generics to be reviewed?

MNTA said they got the letter from the FDA at the end of the day yesterday. They must have had a very long night...

http://ir.momentapharma.com/releasedetail.cfm?ReleaseID=243136
>Momenta Pharmaceuticals Announces Abbreviated New Drug Application Filing for M-Enoxaparin

CAMBRIDGE, Mass., Aug. 30 [2005] /PRNewswire-FirstCall/ -- Momenta Pharmaceuticals, Inc. (Nasdaq: MNTA), announced today that an Abbreviated New Drug Application (ANDA) seeking marketing approval of M-Enoxaparin has been filed with the United States Food and Drug Administration (FDA). Momenta is developing M-Enoxaparin, a technology-enabled generic version of Lovenox®, in collaboration with Sandoz, the generics division of Novartis AG.

Approved for the prevention and treatment of deep vein thrombosis and treatment of acute coronary syndromes, Lovenox (enoxaparin sodium injection) is a widely-prescribed low molecular weight heparin. Sanofi-Aventis reported worldwide Lovenox sales of $2.4 billion in 2004.

"The ANDA for M-Enoxaparin is a major accomplishment for Momenta, representing the first application for marketing approval filed with the FDA based upon our technology," said Alan Crane, Chief Executive Officer of the Company. "We believe that our proprietary approach to characterizing and sequencing complex sugars can be applied to both the development of generic versions of complex drugs as well as to the discovery and development of novel products based on sugars."

Under the FDA's ANDA requirements, a generic drug must be shown to have, among other things, the same active ingredients as the innovator product upon which the generic application is based. Like other low molecular weight heparins, Lovenox consists of a heterogeneous mixture of complex sugar chains. "We believe that our proprietary technology enables us to analyze the Lovenox mixture and demonstrate that M-Enoxaparin has the same active ingredients as Lovenox," said Mr. Crane.<